Soedamah-Muthu Sabita S, Livingstone Shona J, Charlton-Menys Valentine, Betteridge D John, Hitman Graham A, Neil H Andrew W, Bao Weihang, DeMicco David A, Preston Gregory M, Fuller John H, Stehouwer Coen D A, Schalkwijk Casper G, Durrington Paul N, Colhoun Helen M
Division of Human Nutrition, Wageningen University, Bomenweg 2, P.O. Box 8129, 6700 EV, Wageningen, the Netherlands,
Diabetologia. 2015 Jul;58(7):1494-502. doi: 10.1007/s00125-015-3586-8. Epub 2015 Apr 22.
AIMS/HYPOTHESIS: We investigated whether atorvastatin 10 mg daily lowered C-reactive protein (CRP) and whether the effects of atorvastatin on cardiovascular disease (CVD) varied by achieved levels of CRP and LDL-cholesterol.
CRP levels were measured at baseline and 1 year after randomisation to atorvastatin in 2,322 patients with type 2 diabetes (40-75 years, 69% males) in a secondary analysis of the Collaborative Atorvastatin Diabetes Study, a randomised placebo-controlled trial. We used Cox regression models to test the effects on subsequent CVD events (n = 147) of CRP and LDL-cholesterol lowering at 1 year.
After 1 year, the atorvastatin arm showed a net CRP lowering of 32% (95% CI -40%, -22%) compared with placebo. The CRP response was highly variable, with 45% of those on atorvastatin having no decrease in CRP (median [interquartile range, IQR] per cent change -9.8% [-57%, 115%]). The LDL-cholesterol response was less variable, with a median (IQR) within-person per cent change of -41% (-51%, -31%). Baseline CRP did not predict CVD over 3.8 years of follow-up (HRper SD log 0.89 [95% CI 0.75, 1.06]), whereas baseline LDL-cholesterol predicted CVD (HRper SD 1.21 [95% CI 1.02, 1.44]), as did on-treatment LDL-cholesterol. There was no significant difference in the reduction in CVD by atorvastatin, with above median (HR 0.57) or below median (HR 0.52) change in CRP or change in LDL-cholesterol (HR 0.61 vs 0.50).
CONCLUSIONS/INTERPRETATION: CRP was not a strong predictor of CVD. Statin efficacy did not vary with achieved CRP despite considerable variability in CRP response. The use of CRP as an indicator of efficacy of statin therapy on CVD risk in patients with type 2 diabetes is not supported by these data. Trial registration NCT00327418.
目的/假设：我们研究了每日服用10毫克阿托伐他汀是否能降低C反应蛋白（CRP），以及阿托伐他汀对心血管疾病（CVD）的影响是否因CRP和低密度脂蛋白胆固醇（LDL-C）的达标水平而异。
在一项随机安慰剂对照试验——阿托伐他汀糖尿病协作研究的二次分析中，对2322例2型糖尿病患者（40 - 75岁，69%为男性）在基线及随机分组接受阿托伐他汀治疗1年后测量CRP水平。我们使用Cox回归模型来检验1年后CRP和LDL-C降低对后续CVD事件（n = 147）的影响。
1年后，与安慰剂相比，阿托伐他汀组的CRP净降低了32%（95%置信区间 - 40%，- 22%）。CRP反应高度可变，45%服用阿托伐他汀的患者CRP没有降低（中位数[四分位间距，IQR]百分比变化 - 9.8% [- 57%，115%]）。LDL-C反应的变异性较小，个体内中位数（IQR）百分比变化为 - 41%（- 51%，- 31%）。在3.8年的随访中，基线CRP不能预测CVD（每标准差对数的风险比[HR]为0.89 [95%置信区间0.75，1.06]），而基线LDL-C可预测CVD（每标准差HR为1.21 [95%置信区间1.02，1.44]），治疗期间的LDL-C也是如此。阿托伐他汀降低CVD的效果在CRP变化高于中位数（HR 0.57）或低于中位数（HR 0.52），以及LDL-C变化（HR 0.61对0.50）时没有显著差异。
结论/解读：CRP不是CVD的强预测指标。尽管CRP反应存在很大变异性，但他汀类药物的疗效并不随CRP的达标情况而变化。这些数据不支持将CRP用作2型糖尿病患者他汀类药物治疗对CVD风险疗效的指标。试验注册号：NCT00327418
